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Journal of Nuclear Medicine : Official... Jun 2023Radiolabeled antibody treatment with I-omburtamab, administered intraventricularly into the cerebrospinal fluid (CSF) space, can deliver therapeutic absorbed doses to...
Radiolabeled antibody treatment with I-omburtamab, administered intraventricularly into the cerebrospinal fluid (CSF) space, can deliver therapeutic absorbed doses to sites of leptomeningeal disease. Assessment of distribution and radiation dosimetry is a key element in optimizing such treatments. Using a theranostic approach, we performed pretreatment I-omburtamab imaging and dosimetric analysis in patients before therapy. Whole-body planar images were acquired 3 ± 1, 23 ± 2, and 47 ± 2 h after intracranioventricular administration of 75 ± 5 MBq of I-omburtamab via an Ommaya reservoir. Multiple blood samples were also obtained for kinetic analysis. Separate regions of interest (ROIs) were manually drawn to include the lateral ventricles, entire spinal canal CSF space, and over the whole body. Count data in the ROIs were corrected for background and physical decay, converted to activity, and subsequently fitted to an exponential clearance function. The radiation absorbed dose was estimated to the CSF, separately to the spinal column and ventricles, and to the whole body and blood. Biodistribution of the injected radiolabeled antibody was assessed for all patients. Ninety-five patients were included in the analysis. Biodistribution showed prompt localization in the ventricles and spinal CSF space with low systemic distribution, noted primarily as hepatic, renal, and bladder activity after the first day. Using ROI analysis, the effective half-lives were 13 ± 11 h (range, 5-75 h) for CSF in the spinal column, 8 ± 3 h (range, 3-17 h) for ventricles, and 41 ± 11 (range, 23-81 h) for the whole body. Mean absorbed doses were 0.63 ± 0.38 cGy/MBq (range, 0.24-2.25 cGy/MBq) for CSF in the spinal column, 1.03 ± 0.69 cGy/MBq (range, 0.27-5.15 cGy/MBq) for the ventricular CSF, and 0.45 ± 0.32 mGy/MBq (range, 0.05-1.43 mGy/MBq) for the whole body. Pretherapeutic imaging with I-omburtamab allows assessment of biodistribution and dosimetry before the administration of therapeutic activity. Absorbed doses to the CSF compartments and whole body derived from the widely applicable serial I-omburtamab planar images had acceptable agreement with previously reported data determined from serial I-omburtamab PET scans.
Topics: Humans; Kinetics; Tissue Distribution; Radioimmunodetection; Radiometry; Antibodies, Monoclonal
PubMed: 36759197
DOI: 10.2967/jnumed.122.265131 -
Frontiers in Oncology 2022Olfactory neuroblastoma is a rare neoplasm that usually presents in the upper nasal cavity. Although its prognosis is highly unfavorable, effective treatment options are...
Olfactory neuroblastoma is a rare neoplasm that usually presents in the upper nasal cavity. Although its prognosis is highly unfavorable, effective treatment options are still lacking. Moreover, there is no standard treatment for patients with olfactory neuroblastoma that progressed to leptomeningeal carcinomatosis. Here we report an uncommon case of a 59-year-old woman who was diagnosed with olfactory neuroblastoma and leptomeningeal carcinomatosis. For a direct delivery of the drugs to the tumor, and to avoid the impact of lumbar puncture on the patient's quality of life, the intravenous chemotherapy plus intrathecal administration of MTX an Ommaya reservoir was chosen. The results were striking, with the disappearance of tumor cells in the cerebrospinal fluid and the relief of the patient's symptoms with PR. Our result indicates that chemotherapy an Ommaya reservoir offers a new potential therapy for patients with meningeal metastases.
PubMed: 36713576
DOI: 10.3389/fonc.2022.1060575 -
Clinical Lung Cancer Mar 2023Leptomeningeal metastasis (LM) is a highly fatal and debilitating complication of lung adenocarcinoma (LUAD) with limited therapeutic options. This study aimed to...
Safety, Pharmacokinetic and Clinical Activity of Intrathecal Chemotherapy With Pemetrexed via the Ommaya Reservoir for Leptomeningeal Metastases From Lung Adenocarcinoma: A Prospective Phase I Study.
INTRODUCTION
Leptomeningeal metastasis (LM) is a highly fatal and debilitating complication of lung adenocarcinoma (LUAD) with limited therapeutic options. This study aimed to evaluate the efficacy and toxicities of intrathecal chemotherapy (IC) with pemetrexed via Ommaya reservoir in LUAD with refractory LM.
METHODS
In this prospective, single-arm, phase I trial (ChiCTR2000028936), LUAD-LM patients who had progressed after at least two prior treatments were recruited. Pemetrexed from 30 mg to 50 mg was administered on Days 1 and 8 every 3 weeks via Ommaya reservoir. Serial samples of cerebrospinal fluid (CSF) and plasma were obtained for pharmacokinetic studies. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and therapeutic toxicities.
RESULTS
Twenty-three patients were enrolled and analyzed, revealing an ORR of 43.5% (95% CI, 23.2%-63.8%) and DCR of 82.6% (95% CI, 61.2%-95.0%). The median PFS and OS were 6.3 and 9.5 months, respectively. Dose-limiting toxicity was only observed in 2 patients (2/23, 8.7%), and 30 mg pemetrexed was considered as the recommended dose for IC. Pharmacokinetic analysis showed that using Ommaya reservoirs, higher pemetrexed concentrations and prolonged half-lives were achieved in the CSF compared with lumbar puncture (LP).
CONCLUSIONS
Intrathecal pemetrexed at a dose of 30 mg via Ommaya reservoirs on Days 1 and 8 every 21 days achieved promising disease control and satisfactory survival with moderate toxicities in resistant LUAD-LM, providing a feasible and effective option, especially for the patients who cannot tolerate LP.
Topics: Humans; Pemetrexed; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Prospective Studies; Adenocarcinoma of Lung; Meningeal Carcinomatosis; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36588048
DOI: 10.1016/j.cllc.2022.11.011 -
Child's Nervous System : ChNS :... Mar 2023Type I Chiari malformation (CM-I) is a common congenital malformation, often accompanied by syringomyelia. Obstruction of CSF circulation in the foramen magnum is the...
INTRODUCTION
Type I Chiari malformation (CM-I) is a common congenital malformation, often accompanied by syringomyelia. Obstruction of CSF circulation in the foramen magnum is the reason for the formation of the syringomyelia. Fourth ventricle stenting (FVS) could ensure the CSF flow from the fourth ventricle, which might represent an effective approach to achieve syringomyelia relief.
METHODS
We have reviewed four cases of CM-I children who received FVS implantation from November 2021 to July 2022. Each of the patients underwent FMD. The ventricular catheter of an Ommaya reservoir (Medtronic, Inc.) was used as a stent. Duraplasty was performed with autologous fascia. Cervical MRI rechecks were routinely done 3 months later, and the clinical symptoms were followed up.
RESULTS
Four children received FVS, including one boy and three girls, aged from 12 months to 10 years, with a mean age of 6.8 years. No major complication occurred. The syringomyelia or hydrocephalus in each patient were all attenuated, as observed on the reexamination MRI images. During the follow-up time with a mean of 10.8 months, no patient had new symptoms.
CONCLUSION
FVS is an effective and safe method for operation of CM-1 in children. The indications of FVS include redo-FMD, difficulties to ensure post-FMD CSF circulation patency at the foramen magnum and with obstructive hydrocephalus. A long-term follow-up duration is necessary.
Topics: Male; Female; Humans; Child; Syringomyelia; Fourth Ventricle; Decompression, Surgical; Arnold-Chiari Malformation; Magnetic Resonance Imaging; Hydrocephalus; Stents; Treatment Outcome
PubMed: 36572815
DOI: 10.1007/s00381-022-05793-0 -
Neurological Research Apr 2023Neuroendoscopic resection supracerebellar infratentorial (SCIT) approach is adequate for some indicated pineal region tumors with the natural infratentorial corridor.... (Review)
Review
OBJECTIVE
Neuroendoscopic resection supracerebellar infratentorial (SCIT) approach is adequate for some indicated pineal region tumors with the natural infratentorial corridor. We described this full endoscopic approach through a modified 'head-up' park-bench position to facilitate the procedure.
METHODS
We reviewed the clinical and radiological data of four patients with pineal region lesions who underwent pure endoscopic tumor resection through the SCIT approach with this modified position. The related literature concerning fully endoscopic pineal region tumor resection was also reviewed.
RESULTS
This cohort included four patients with pineal region tumors. External ventricular drainage (Ommaya reservoir) was performed in three patients with hydrocephalus in advance. The average tumor volume was 19.2 ± 17.2 cm. Pathological examination confirmed two mixed germinomas, one glioblastoma multiforme, and one hemangioblastoma. Gross total resection (GTR) was achieved in all patients, and all patients recovered well without neurological deficits or surgical complications. Hydrocephalus was relieved among all patients.
CONCLUSIONS
The pure endoscopic SCIT approach could enable safe and effective resection of pineal region tumors, even for relatively large lesions. The endoscope could provide a panoramic view and illumination of the deep-seated structures. Compared with the sitting position, this modified ergonomic position could be implemented easily.
Topics: Humans; Sitting Position; Neurosurgical Procedures; Pinealoma; Pineal Gland; Neuroendoscopy; Brain Neoplasms
PubMed: 36509700
DOI: 10.1080/01616412.2022.2146266 -
British Journal of Neurosurgery Dec 2022Total resection of cystic craniopharyngiomas is challenging, especially for some large cystic tumors, because it is often associated with high recurrence and morbidity...
INTRODUCTION
Total resection of cystic craniopharyngiomas is challenging, especially for some large cystic tumors, because it is often associated with high recurrence and morbidity rates. Minimally invasive cyst decompression and continuous drainage are appropriate to manage clinical symptoms. We reviewed our experience of the past 11 years to determine the long-term effects of neuroendoscopic surgery (NES) combined with Ommaya reservoir (OR) for the treatment of cystic craniopharyngiomas.
METHODS
We retrospectively analyzed the data of 15 adult patients with cystic craniopharyngiomas at a single institution with the primary goal to evaluate the treatment mode with initial adequate decompression of the cyst under visualization and continuous drainage. The study endpoints were functional outcome, cyst volume changes, and tumor progression.
RESULTS
The median follow up was 77 (20-136) months. Clinical symptoms, e.g. increased intracranial pressure and visual impairment, could be rapidly improved after NES. The postoperative reduction in cyst volume ( < 0.001) and improvement in Karnofsky performance status ( < 0.001) were significant, and long-term tumor control was achieved in 10 patients (67%). Aspiration from the OR after progression of the tumor's cystic portion remains a major option, with only few patients requiring repeat NES procedures. No patient developed acute or severe clinical symptoms during follow up.
CONCLUSIONS
NES could decompress the craniopharyngioma cyst under visualization and enable faster clinical-symptom improvement. The minimally invasive NES combined with OR allowed long-term symptom control in most patients without surgery-related injury. This palliative treatment strategy could be an alternative modality for cystic craniopharyngioma treatment.
PubMed: 36469601
DOI: 10.1080/02688697.2022.2152776 -
No Shinkei Geka. Neurological Surgery Nov 2022Childhood hydrocephalus is a highly diverse disease caused by various factors, and most surgical treatments are performed during infancy. Despite the diversity of...
Childhood hydrocephalus is a highly diverse disease caused by various factors, and most surgical treatments are performed during infancy. Despite the diversity of hydrocephalus pathologies, treatment options are limited. It is difficult for pediatric neurosurgeons to select and perform appropriate surgical procedures for neonates and infants. Treatment options for hydrocephalus are broadly divided into permanent and temporary. Permanent treatments include cerebrospinal fluid shunt and endoscopic third ventriculostomy; temporary treatment entails cerebrospinal fluid drainage using lumbar puncture and intermittent cerebrospinal fluid drainage with an Ommaya reservoir, ventricular drainage, and ventriculosubgaleal shunt. This article describes in detail Ommaya reservoir placement and ventricular drainage as representative procedures for temporarily treating hydrocephalus.
Topics: Infant, Newborn; Infant; Humans; Child; Cerebral Hemorrhage; Retrospective Studies; Hydrocephalus; Drainage; Cerebrospinal Fluid Leak
PubMed: 36426516
DOI: 10.11477/mf.1436204682 -
Brain Tumor Research and Treatment Oct 2022Intra-cerebrospinal fluid (CSF) chemotherapy for leptomeningeal metastasis (LM) can be delivered intraventricularly via an Ommaya reservoir. However, hydrocephalus...
BACKGROUND
Intra-cerebrospinal fluid (CSF) chemotherapy for leptomeningeal metastasis (LM) can be delivered intraventricularly via an Ommaya reservoir. However, hydrocephalus associated with LM can interfere with chemotherapeutic drug distribution, and ventriculoperitoneal shunts can prevent drug distribution to the extra-ventricular CSF space. This study examined the feasibility of combining a lumboperitoneal (LP) shunt with an Ommaya reservoir to both control intracranial pressure and allow for intraventricular chemotherapy.
METHODS
We identified 16 patients with LM who received both an Ommaya reservoir and an LP shunt, either concurrently or sequentially, and subsequently received intraventricular chemotherapy. The feasibility of this combination for intraventricular chemotherapy was evaluated by assessing 1) the distribution of intraventricularly injected drugs in CSF samples collected 0, 6, and 12 h post-injection and 2) adverse events associated with the procedure and drug administration.
RESULTS
Patients received a median of seven rounds (range 1-37) of intraventricular chemotherapy during a median follow-up period of 5.2 months after LP shunt insertion. Pharmacokinetic data were obtained from six patients. Baseline methotrexate (MTX) levels from Ommaya reservoirs varied from 339.9 µM to 1,523.5 µM. CSF sampled from LP shunt reservoirs revealed an elimination half-life (t) of 2.63 h, and the mean ratio of MTX concentration at 12 h to that at baseline was 0.05±0.05, ensuring drug distribution from the ventricle to the spinal canal. Nine patients (56%) underwent revision surgery due to catheter migration, malfunction, or infection. Among these patients, CSF infections attributable to intraventricular chemotherapy (n=3) occurred, but no infections occurred in later cases after we began to employ a complete aseptic technique.
CONCLUSION
LP shunt combined with Ommaya reservoir insertion is a feasible option for achieving both intracranial pressure control and the continuation of intraventricular chemotherapy in patients with LM.
PubMed: 36347638
DOI: 10.14791/btrt.2022.0022 -
Frontiers in Neurology 2022Glioma is the most common primary brain tumor in adults with poor prognosis. The glioma patients benefit from STUPP strategy, including maximum and safe resection and...
BACKGROUND
Glioma is the most common primary brain tumor in adults with poor prognosis. The glioma patients benefit from STUPP strategy, including maximum and safe resection and adjuvant radiotherapy and chemotherapy. Arsenic trioxide could inhibit various tumors. However, it is a challenge to evaluate the efficiency and safety of srsenic trioxide in glioma patients.
OBJECTIVE
The arsenic trioxide has the potent therapeutic effect on glioma. However, the safety and efficacy of local interstitial chemotherapy with arsenic trioxide in newly diagnosed glioma patients is unclear.
METHODS
All patients received partial or complete tumor resection and intraoperative implantation of Ommaya reservoirs followed by standard radiotherapy. Arsenic trioxide with the starting dose 0.3 mg was administered an Ommaya reservoir catheter inserted into the tumor cavity for 5 consecutive days every 3 months for a total of eight cycles unless tumor progression or excessive toxicity was observed.
RESULTS
No hematological or grade 4 non-hematological toxicity was observed in any patient during arsenic trioxide treatment. The maximum tolerated dose of 1.5 mg of arsenic trioxide was safe and well tolerated. The median overall survival for WHO grade 3 glioma was 33.6 months, and for glioblastoma was 13.9 months. The median progression-free survival for WHO grade 2 glioma was 40.3 months, for grade 3 glioma was 21.5 months, and for glioblastoma was 9.5 months.
CONCLUSION
These results suggest that arsenic trioxide is safe and well tolerated with local delivery into the tumor cavity of the brain, and the dose recommended for a phase II trial is 1.5 mg.
PubMed: 36212657
DOI: 10.3389/fneur.2022.1001829 -
Journal of Neurosurgery. Case Lessons Mar 2022Treatment of pilocytic astrocytomas (PAs) in children can be challenging when they arise in deep midline structures because complete surgical resection may result in...
BACKGROUND
Treatment of pilocytic astrocytomas (PAs) in children can be challenging when they arise in deep midline structures because complete surgical resection may result in significant neurological injury. Laser interstitial thermal therapy (LITT) has provided an alternative treatment modality for lesions that may not be amenable to resection. However, many patients with PAs may be symptomatic from a compressive cyst associated with the PA, and LITT does not obviate the need for cystic decompression in these patients.
OBSERVATIONS
A 12-year-old male presented with left-sided weakness. Magnetic resonance imaging (MRI) revealed an enhancing mass with a large cyst involving the right thalamus and basal ganglia. The patient underwent a reservoir placement for cyst drainage and biopsy of the mass, revealing a pilocytic astrocytoma. He then underwent LITT followed by adjuvant chemotherapy. Sixteen months after LITT, follow-up MRI of the brain revealed no tumor growth.
LESSONS
This is the first case to describe reservoir placement to treat the cystic portion of a pilocytic astrocytoma followed by LITT and targeted chemotherapy. Reservoir placement reduced the cyst's mass effect and resolved the patient's symptoms, allowing for treatment options beyond resection.
PubMed: 36209402
DOI: 10.3171/CASE21363